Biology and pathogenesis of human herpesviruses

Herpesviruses are large, complex viruses with double-stranded DNA genomes encoding about 70 to 170 genes. There are eight known human herpesviruses and the majority of adults are persistently infected with six of them. Infection of immunocompetent individuals usually results in mild symptoms, but the outcome can be serious when the immune system is damaged or inadequate. Following primary infection, herpesviruses persist for the lifetime of the host in a latent state from which they can reactivate to cause recurrent disease. Herpesvirus infections impose a serious clinical and economic burden on society and there is a pressing need for the development of new vaccines, antiviral agents and diagnostic tools. Research in the CVR focusses on human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and varicella-zoster virus (VZV).

HCMV studies are investigating the early events after infection, with emphasis on the control of viral transcription and the role of host responses in virus-related diseases. In addition, the molecular epidemiology and cell tropism of HCMV is being analysed, focussing on the virus as it exists in humans. In complementary studies, the biological basis and clinical significance of a correlation between HLA-A genotype and EBV-associated Hodgkin lymphoma, and other diseases, is under investigation and we are using transgenic models to explore the mechanism of action of EBV gene products in tumourigenesis and immune evasion. CVR researchers are also examining the host and viral factors involved in VZV-associated diseases, particularly post-herpetic neuralgia.